The protective effect of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats

The purpose of the present study is to investigate the protective effect of calcitonin gene-related peptide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting. After regaining consciousness from the anaesthesia,rats were scored according to Zea longa 5 score system. Animals with scores 1-3 were randomly divided into two groups：CGRP group and normal saline group（NS group）. Sham-operated animals were stimulated only by the operation without occluding the middle cerebral artery. Ten rats were involved in each group. Reperfusion was given to the rats in CGRP group and NS group after 2 hours’ ischemia. Rats in CGRP group and NS group were injected intraperiloneally with CGRP (3μg/kg,1mg/L) or NS(3ml/kg) respectively. After 48 hours of the operation,the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method,detecting pathological changes of gastric mucosa tissue by light microscopy,determining mast cells by toluidine blue staining,and observing the expression of Gas, SST, AQP-4 and bFGF by immunohistochemical staining. One-way analysis of variance was used for statistical analysis. Difference between two groups was compared with qtest. Results：1. Under stereo microscope, focal cerebral ischemia and reperfusion rat more significant damage of gastric mucosa of NS group than that of CGRP group was observed,with diffuse edema,splinter hemorrhage and erosion. The injury index of gastric mucosa was lower in CGRP group as compared with that in NS group (P<0.05). 2. HE staining showed that under light microscope,gastric mucosa was damaged more pronouncedly with numerous endothelial cells necrosis,gastric mucosa dissociation,infiltration of inflammatory cells,and irregular arrangement of glands,while in CGRP group,the damage was less severe with partially dissociation of gastric mucosa,less irregular arrangement of glands,fewer mucosa hemorrhage and inflammatory cells infiltration. 3. The total number of mast cells and degranulation ratio of NS group in gastric mucosa was significantly higher than that of CGRP group (P<0.01). 4. Gas expression in gastric antrum mucosa was lower in CGRP group than that in NS group (P<0.01);SST expression in gastric antrum mucosa was higher in CGRP group than that in NS group (P<0.01). 5. AQP-4 expression in gastric mucosa was lower in CGRP group than that in NS group (P<0.05). 6. bFGF expression in gastric mucosa was higher in CGRP group than that in NS group (P<0.01). The results indicated that CGRP reduced the gastric mucosa injury index after brain ischemia and reperfusion,alleviated the damage of gastric mucosa and thus had protective effect on the stomach. An indirect protective effect of CGRP on gastric mucosa was also noted by the up-regulated SST expression and down-regulated Gas expression. CGRP down-regulated AQP-4 expression and up-regulated bFGF expression reduced gastric edema,regulated the secretion of gastric acid and exerted to promote gastric tissue repair. Besides,CGRP also inhibited mast cell degaranulation to reduce the infiltration of inflammatory cells and thus to alleviate the damage of gastric mucosa induced by ischemia and reperfusion.